ArticleThe Journal of clinical investigation2020
Caspase-11-mediated enteric neuronal pyroptosis underlies Western diet-induced colonic dysmotility.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.CNS neuroscience & therapeutics · 2026Pooled it
- Article
- Fusobacterium nucleatum enhances enterotoxigenic Bacteroides fragilis-mediated neuron loss and intestinal motility dysfunction.Nature microbiology · 2026Article
- Western diet induces iron-dependent enteric neurodegeneration via ferroptosis.The Journal of clinical investigation · 2026Article
- A new paradigm: 46 structural cell types function as environment-supporting innate immune cells, with endothelial and vascular smooth muscle cells as key prototypes.iNew medicine · 2026Article
- Differential Effects of Saturated and Unsaturated Fatty Acids on Colorectal Cancer via IDO1 Signaling.Cancer medicine · 2026Article
- CARD14 signaling in intestinal epithelial cells induces intestinal inflammation and intestinal transit delay.EMBO molecular medicine · 2025Article
- Small Intestine Neuromuscular Dysfunctions and Neurogliopathy in a Mouse Model of High-Fat Diet-Induced Obesity: Involvement of Toll-Like Receptor 4.International journal of molecular sciences · 2025Article
- Regulatory Roles of Noncanonical Inflammasomes in Diabetes Mellitus and Diabetes-Associated Complications.International journal of molecular sciences · 2025Review
- Mechanisms of enteric neuropathy in diverse contexts of gastrointestinal dysfunction.Neurogastroenterology and motility · 2025Review
- Chaperone-mediated autophagy, heat shock protein 70, and serotonin: novel targets of beta-hydroxybutyrate in HFFD/LPS-induced sporadic Alzheimer's disease model.Inflammopharmacology · 2025Article
- Article
- GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- To die or not to die: Gasdermins in intestinal health and disease.Seminars in immunology · 2024Review
- To explore the postoperative nutritional status and factors influencing prognosis in patients with chronic constipation complicated by malnutrition.Frontiers in medicine · 2024Article
- Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons.International journal of biological sciences · 2024Article
- Article
- Amyloid-β mediates intestinal dysfunction and enteric neurons loss in Alzheimer's disease transgenic mouse.Cellular and molecular life sciences : CMLS · 2023Article
- Angelica acutiloba Kitagawa flower induces A549 cell pyroptosis via the NF-κB/NLRP3 pathway for anti-lung cancer effects.Cell division · 2023Article
- Novel Mechanisms of Perioperative Neurocognitive Disorders: Ferroptosis and Pyroptosis.Neurochemical research · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Enteric neuronal degeneration, as seen in inflammatory bowel disease, obesity, and diabetes, can lead to gastrointestinal dysmotility. Pyroptosis is a novel form of programmed cell death but little is known about its role in enteric neuronal degeneration. We observed higher levels of cleaved caspase-1, a marker of pyroptosis, in myenteric ganglia of overweight and obese human subjects compared with normal-weight subjects. Western diet-fed (WD-fed) mice exhibited increased myenteric neuronal pyroptosis, delayed colonic transit, and impaired electric field stimulation-induced colonic relaxation responses. WD increased TLR4 expression and cleaved caspase-1 in myenteric nitrergic neurons. Overactivation of nitrergic neuronal NF-κB signaling resulted in increased pyroptosis and delayed colonic motility. In caspase-11-deficient mice, WD did not induce nitrergic myenteric neuronal pyroptosis and colonic dysmotility. To understand the contributions of saturated fatty acids and bacterial products to the steps leading to enteric neurodegeneration, we performed in vitro experiments using mouse enteric neurons. Palmitate and lipopolysaccharide (LPS) increased nitrergic, but not cholinergic, enteric neuronal pyroptosis. LPS gained entry to the cytosol in the presence of palmitate, activating caspase-11 and gasdermin D, leading to pyroptosis. These results support a role of the caspase-11-mediated pyroptotic pathway in WD-induced myenteric nitrergic neuronal degeneration and colonic dysmotility, providing important therapeutic targets for enteric neuropathy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.